title: 'Decoy' and 'non-decoy' functions of DcR3 promote malignant potential in human malignant fibrous histiocytoma cells.
abstract: Decoy receptor 3 (DcR3) is a soluble secreted protein that belongs to the tumor necrosis factor receptor (TNFR) superfamily. DcR3 inhibits the Fas ligand (FasL)/Fas apoptotic pathway by binding to FasL, competitively with Fas receptor. Previous studies have reported that overexpression of DcR3 has been detected in various human malignancies and that DcR3 functions as a 'decoy' for FasL to inhibit FasL-induced apoptosis. In addition, recent studies have revealed that DcR3 has 'non-decoy' functions to promote tumor cell migration and invasion, suggesting that DcR3 may play important roles in tumor progression by decoy and non-decoy functions. We have previously reported that overexpression of DcR3 was observed in human malignant fibrous histiocytoma (MFH), however, the roles of DcR3 in MFH have not been studied. In the present study, to elucidate the roles of DcR3 in tumor progression of MFH, we examined the effects of DcR3 inhibition on cell apoptosis, migration and invasion in human MFH cells. siRNA knockdown of DcR3 enhanced the FasL-induced apoptotic activity and significantly decreased cell migration and invasion with a decrease in the activation of phosphatidylinositol 3 kinase (PI3K)/Akt and matrix metalloproteinase (MMP)-2. The findings in this study strongly suggest that DcR3 plays important roles in tumor progression of human MFH by decoy as well as non-decoy functions and that DcR3 may serve as a potent therapeutic target for human MFH.
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Toda
authors.forename: Teruya
authors.initials: T
authors.lastname: Kawamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ueha
authors.forename: Kenta
authors.initials: K
authors.lastname: Kishimoto
authors.forename: Hitomi
authors.initials: H
authors.lastname: Hara
authors.forename: Naomasa
authors.initials: N
authors.lastname: Fukase
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Onishi
authors.forename: Risa
authors.initials: R
authors.lastname: Harada
authors.forename: Masaya
authors.initials: M
authors.lastname: Minoda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurosaka
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Akisue
mesh_terms: D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis; D053222:Fas Ligand Protein; D015972:Gene Expression Regulation, Neoplastic; D051677:Histiocytoma, Malignant Fibrous / Q000235:genetics* / Q000473:pathology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D058990:Molecular Targeted Therapy; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000037:antagonists & inhibitors / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D053222:Fas Ligand Protein; D034741:RNA, Small Interfering; D053323:Receptors, Tumor Necrosis Factor, Member 6b; C505911:TNFRSF6B protein, human; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2